First patients shown to improve with embryonic stem cells
Before treatment, the 51-year-old graphic artist was legally blind, unable to read a single letter on a standard eye chart. She has suffered from Stargardt’s disease, the most common form of macular degeneration in young patients, since she was a teenager, and it was getting progressively worse.
A second patient, aged 78, suffered from dry macular degeneration - the leading cause of blindness in the elderly - and could not even see well enough to go shopping.
But after being treated with stem cells from a donated human embryo, both women have improved dramatically, researchers said on Monday. Stem cells are master cells that can differentiate into any of the 200 kinds of cells in the human body.
Their results are the first-ever report of the medical use of stem cells taken from human embryos, making them crucial barometers of whether the controversial technique will ever find widespread therapeutic uses.
In a paper published online in The Lancet on Monday, physicians at the University of California, Los Angeles, and scientists at biotechnology company Advanced Cell Technology report that the first two patients in the clinical trial suffered no adverse health effects from the treatment and seem to have benefited from it.
A week after having cells derived from a days-old embryo injected into her eye, the graphic artist could count fingers, and after one month she could read the top five letters on the eye chart. She can see more color and contrast, has started using her computer, and for the first time in years can read her watch and thread a needle. The macular degeneration patient recently went to the mall for the first time in years.
What are embryonic stem cells?
A. What stages of early embryonic development are important for generating embryonic stem cells?
Embryonic stem cells, as their name suggests, are derived from embryos. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman’s body.
B. How are embryonic stem cells grown in the laboratory?
Growing cells in the laboratory is known as cell culture. Human embryonic stem cells (hESCs) are generated by transferring cells from a preimplantation-stage embryo into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. The inner surface of the culture dish is typically coated with mouse embryonic skin cells that have been treated so they will not divide. This coating layer of cells is called a feeder layer. The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach. Also, the feeder cells release nutrients into the culture medium. Researchers have devised ways to grow embryonic stem cells without mouse feeder cells. This is a significant scientific advance because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells.
The process of generating an embryonic stem cell line is somewhat inefficient, so lines are not produced each time cells from the preimplantation-stage embryo are placed into a culture dish. However, if the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of re-plating or subculturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell line is established, the original cells yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for for a prolonged period of time without differentiating, are pluripotent, and have not developed genetic abnormalities are referred to as an embryonic stem cell line. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.
The safety findings, not any vision improvement, is what people should focus on, said Dusko Ilic, senior lecturer in stem cell science at Kings College London, who was not involved in the work.
“If everyone expects that the blind patients will see after being treated ... it will end up as disaster,” he said.
Nevertheless, advocates for the blind are already hailing the results. “At last we are seeing fruits of human embryonic stem cell research entering clinical trials,” said Peter Coffey, Director of the London Project to Cure Blindness.
OBJECTIONS AND RISKS
Using human embryonic stem cells for research or treatment has incited controversy for ethical and medical reasons. Some opponents argue that because removing stem cells from days-old human embryos almost always destroys the embryo, the technique amounts to murder.
“This is a big step forward for regenerative medicine, said Dr. Steven Schwartz at UCLA’s Jules Stein Eye Institute. “It’s nowhere near a treatment for vision loss, but it’s a signal that embryonic stem-cell based strategies may work.”
Schwartz added several caveats - that the study was preliminary, only in two patients, and that it’s difficult to measure vision in low-vision patients. But even so he was “thrilled and excited” about the study.
ACT is the only company currently testing human embryonic stem cells in study patients. Last November, stem-cell pioneer Geron announced that it was halting what had been the first-ever clinical trial of the cells-testing them in patients with spinal cord injuries - and leaving the field.
When Robert Lanza, chief scientific officer of ACT, approached ophthalmic surgeon Steven Schwartz of UCLA about leading the clinical trial, Schwartz asked for ethical advice from two of his patients: elderly nuns. They gave him the go-ahead, he said last year.
Even scientists who support stem cell research argue that they could be dangerous to use therapeutically. The very property that makes them so valuable in research - stem cells can morph into any of the kinds of cells in the human body - also makes them risky.
They can form teratomas, a type of tumor that arises when stem cells differentiate into a profusion of cell types.
Another concern is that transplanting cells derived from human embryos could be rejected by the patient’s immune system. The ACT team got around that by targeting the eye, which is an “immunoprivileged” site that does not produce a strong immune response to foreign tissue.
In the study, physicians led by Schwartz injected what are called retinal epithelial cells into one eye of each patient. RPE cells lie at the back of the eye and bathe the retina’s rods and cones in substances called growth factors. When RPE cells die, as they do in macular degeneration, so do the photoreceptors, eventually causing blindness.